Ultrasonic vocalizations during intermittent swim stress forecasts resilience in subsequent forced swim and spatial learning tests.

The examination of stress resilience has substantially increased in recent years. However, current paradigms require multiple behavioral procedures, which themselves may serve as secondary stressors. Therefore, a novel predictor of stress resilience is needed to advance the field. Ultrasonic vocalizations (USVs) have been observed as a behavioral correlate of stress in various rodent species. It was recently reported that rats that emitted ultrasonic vocalizations during intermittent swim stress (ISS) later showed resilience when tested on an instrumental swim escape test. In the current study, we extend this earlier observation on two additional behavioral endpoints. Rats were subjected to ISS, and USVs were recorded. Twenty-four hours later, behavioral performance was evaluated in either the forced swim test or Morris water maze. Rats that emitted ultrasonic vocalizations were resilient to the effects of ISS as indicated by performance similar to controls on both measures. These results extend the original findings that ISS-induced USVs are associated with resilience and are related to subsequent aversively motivated behavior. Such a non-invasive forecast of stress responsivity will allow future work to utilize USVs to examine the neural correlates of initial stress resistance/resilience, thereby eliminating potential confounds of further behavioral testing. Future studies can utilize USVs to target potentially unappreciated neural systems to provide novel pharmacotherapeutic strategies for treatment-resistant depression.

Metabolic products of [2-(13) C]ethanol in the rat brain after chronic ethanol exposure.

Most ingested ethanol is metabolized in the liver to acetaldehyde and then to acetate, which can be oxidized by the brain. This project assessed whether chronic exposure to alcohol can increase cerebral oxidation of acetate. Through metabolism, acetate may contribute to long-term adaptation to drinking. Two groups of adult male Sprague-Dawley rats were studied, one treated with ethanol vapor and the other given room air. After 3 weeks the rats received an intravenous infusion of [2-(13) C]ethanol via a lateral tail vein for 2 h. As the liver converts ethanol to [2-(13) C]acetate, some of the acetate enters the brain. Through oxidation the (13) C is incorporated into the metabolic intermediate α-ketoglutarate, which is converted to glutamate (Glu), glutamine (Gln), and GABA. These were observed by magnetic resonance spectroscopy and found to be (13) C-labeled primarily through the consumption of ethanol-derived acetate. Brain Gln, Glu, and, GABA (13) C enrichments, normalized to (13) C-acetate enrichments in the plasma, were higher in the chronically treated rats than in the ethanol-naïve rats, suggesting increased cerebral uptake and oxidation of circulating acetate. Chronic ethanol exposure increased incorporation of systemically derived acetate into brain Gln, Glu, and GABA, key neurochemicals linked to brain energy metabolism and neurotransmission. The liver converts ethanol to acetate, which may contribute to long-term adaptation to drinking. Astroglia oxidize acetate and generate neurochemicals, while neurons and glia may also oxidize ethanol. When (13) C-ethanol is administered intravenously, (13) C-glutamine, glutamate, and GABA, normalized to (13) C-acetate, were higher in chronic ethanol-exposed rats than in control rats, suggesting that ethanol exposure increases cerebral oxidation of circulating acetate.